Dasatinib Is Safe, Effective in Pediatric Chronic Myeloid Leukemia

Dasatinib was safe and effective in pediatric patients with chronic myeloid leukemia (CML), according to a new study, establishing the agent as a new standard of care for this population.

“CML represents less than 3% of all leukemias in children worldwide, and as such a rare disease becomes difficult to study,” said Lia Gore, MD, of the University of Colorado at Denver. She said that more aggressive CML has been seen in children, and that only imatinib is currently approved for these patients. “There is an unmet need for pediatric patients with CML.”

Gore presented results of a phase II trial (abstract 10511) at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago. She reported on two of three cohorts in the CA180-226 trial. The first cohort included 29 chronic-phase CML patients treated with dasatinib tablets; these patients were either imatinib-refractory or -intolerant.

A second cohort (n = 84) included newly diagnosed CML patients, with the first 51 patients receiving dasatinib tablets, and the subsequent 33 patients treated with a powdered formulation for oral suspension (PFOS) form of the drug.

The refractory/intolerant cohort exceeded the major cytogenetic response (MCyR) rate of clinical interest of 30% by the 3-month point of the study, and by 24 months, the rate of MCyR exceeded 90%. The median time to response in these patients was 3.1 months, and the median duration of response had not been reached.

The clinical rate of interest for complete cytogenetic response (CCyR) was 55% for the newly diagnosed patients, and this rate was exceeded at the 6-month time point. At 24 months, the CCyR rate was 94%, with rates above 90% for both the tablet and PFOS forms of dasatinib.

At 24 months, the cumulative rate of major molecular response was 55% in the imatinib-refractory/intolerant patients, and 70% in the newly diagnosed patients (75% with tablet form of dasatinib, 64% with PFOS). The 48-month progression-free survival rate was 78% in the refractory/intolerant patients and 93% in the newly diagnosed patients; the median progression-free survival was not reached. One patient in the refractory/intolerant group died during the study-1 year after treatment cessation-of a gastrointestinal bleed unrelated to the study drug.

Dasatinib-related serious adverse events occurred in 17% of the refractory/intolerant patients, and in 10% of the newly diagnosed patients; only one patient had an adverse event related to the study drug that led to discontinuation (grade 3 drug hypersensitivity). Notably, there were no cases of pleural effusion, pericardial effusion, pulmonary edema, pulmonary hypertension, or pulmonary arterial hypertension.

“We believe our data suggest that dasatinib could be considered as a new standard of care for children with CML in the chronic phase,” Gore concluded, adding that the liquid formulation could also add the advantage of once-daily dosing and administration with or without food.

Elizabeth Fox, MD, of the University of Philadelphia, was the discussant for the session, and she said the obvious question now is whether a randomized trial comparing imatinib and dasatinib in pediatric CML patients is necessary. Given the rarity of the population and these new results, she said, that may reflect an old way of thinking that isn’t useful. “We may need to move on the data we have and consider what is in the best interests of our patients,” she said.